Cancer patients who received antibiotics within 60 days of starting immunotherapy were significantly less likely to respond to cancer treatment than those not receiving antibiotics, according to a research reported at the Gastrointestinal Cancers Symposium 2019 .
“Obviously, antibiotics should be used when indicated, such as for sepsis and other bacterial infections, but we are suggesting that antibiotics should be avoided if there is no clear indication for them,” said investigator Uqba Khan, MD, of NewYork-Presbyterian Hospital/ Weill Cornell Medicine, in New York City.
The results of the study provide an association between the use of antibiotics and inferior outcomes from immunotherapy.
However, he stressed that; “We don’t know whether antibiotics somehow directly cause inferior outcomes from immunotherapy or whether there are other factors involved, as well. This question needs to be further explored.”
There is emerging evidence that the gut microbiome may influence antitumor immune response during treatment with checkpoint inhibitors. The use of antibiotics is among factors that can cause gut microbiome dysbiosis, he said.
Dr. Khan and his co-investigators hypothesized that the use of antibiotics during immunotherapy can adversely affect the efficacy of checkpoint inhibitors. The study conducted an institutional retrospective review of all patients treated with checkpoint inhibitors between 2015 and 2018. The patients, who were prescribed with antibiotics within six months of initiating or completing immunotherapy were studied.
The study identified 76 patients who had taken antibiotics during the six-month period before or after immunotherapy and 166 who had not. Approximately half the patients had lung cancer. For about one-fourth of the patients, the checkpoint inhibitor was a first-line treatment, and the remainder had received other drugs first. Half the patients received pembrolizumab (Keytruda, Merck), and the other half received nivolumab (Opdivo, Bristol-Myers Squibb) or atezolizumab (Tecentriq, Genentech).
The most common antibiotics used were piperacillin-tazobactam, vancomycin and azithromycin.
“Antibiotic use was common,” Dr. Khan said. “We found that 32% of patients had used antibiotics within the first 60 days of starting a checkpoint inhibitor.” In addition, use of antibiotics within 30 or 60 days after the start of treatment with checkpoint inhibitors was associated with significantly lower response rates.
Antibiotic use also was associated with decreased progression-free survival (PFS). Median PFS was 60 days for patients who used antibiotics within 60 days of treatment versus 126 days for non-users, he reported.
The researchers have since evaluated more patients and the results have not changed, he said. They are planning to conduct studies in mouse models to further evaluate the correlation between timing of antibiotic use and outcomes.
“We see patients all the time who have fever. There are guidelines for giving them antibiotics, but the question becomes whether we do so reflexively, without really thinking. This information is very relevant as well to primary care practices. Every primary care physician treats cancer patients for fever, especially during flu season,” said Sandeep Reddy, MD, Chief medical officer at NantHealth, in Culver City, Calif.
“With checkpoint inhibitors, we are often going for a cure,” he pointed out. “We don’t want to blunt the ability to cure these patients because we give antibiotics inappropriately.”he added.